Search PubMed⌕ Search

Biomedical subjects

R Goldstein

Publications and source records attributed to R Goldstein.

At least 163 records · Page 9Linked to original sources
PubMed1990

HLA-D region genes associated with autoantibody responses to histidyl-transfer RNA synthetase (Jo-1) and other translation-related factors in myositis.

Myositis has been associated with HLA-B8 and DR3, especially in white patients with polymyositis and serum anti-Jo-1 antibodies. Twenty-eight patients with myositis and serum translation-related autoantibodies anti-Jo-1, anti-PL-7, anti-PL-12, anti-KJ, and anti-SRP were studied for HLA class II specificities by Southern blotting with HLA-DR beta, DQ beta, and DQ alpha probes. The association of HLA-DR3 (DRw17) with anti-Jo-1 antibodies in white myositis patients was confirmed (P = 0.003, relative risk 8.9). However, HLA-DRw52 haplotypes, regardless of subtype, were present in all of the white and black patients with serum anti-Jo-1 and other translation-related autoantibodies. Moreover, one anti-Jo-1 positive patient had HLA-DRw8, an HLA-DRw52 haplotype on which the DR beta 3 gene has been partially deleted. No HLA-DQ specificity or allele was common to all patients. The HLA-DR3, DR5, DRw6, and DRw8 haplotypes, which bear the HLA-DRw52 specificity, share the most homology in the DR beta 1 first hypervariable region at amino acid positions 9-13. Thus, this DR beta 1 region appears to be the most likely candidate "epitope" for translation-related autoimmune responses in inflammatory myositis.

Alleles↗
PubMed1990

A phasmid shuttle vector for the cloning of complex operons in Salmonella.

Phasmid (phage plasmid hybrid) P4 vir1 can be propagated in Escherichia coli as a helper-dependent lytic phage, as a plasmid, or as a prophage. On the basis of an understanding of these modes of propagation, derivatives of P4 have been constructed for use as cloning vectors. In this report we demonstrate that phasmid P4 (i) will propagate as a helper-dependent lytic phage and as a plasmid in Salmonella spp. and (ii) can be used as a high efficiency phage shuttle vector for the reversible transfer of cloned genes between Salmonella spp. and E. coli. For both E. coli and Salmonella spp., P4 phage-mediated gene transfer proved to be only 10-fold lower than plaquing efficiency. For the case of Salmonella spp., this frequency is ca. 10(4)-fold more efficient than is typically found for the transformation of DNA molecules. The usefulness of this cloning vector system for analyses of pathogenic virulence factors is demonstrated by the cloning and expression of both the P pilus adhesin operon and the hemolysin operon of uropathogenic E. coli.

Cloning, Molecular↗
PubMed1990

Regulation of icosahedral virion capsid size by the in vivo activity of a cloned gene product.

Determination of icosahedral virion capsid size can be directly studied during helper-dependent lytic development of satellite P4 because the assembly pathway specified by the P2 helper virus is altered to yield smaller-sized capsids. Size determination (sid) mutations identify a P4-encoded function regulating this process. To determine whether the sid gene product is necessary and sufficient to redirect the assembly pathway, we (i) cloned the sid structural gene in a plasmid vector (pMA30) under the control of an inducible promoter and (ii) constructed a packaging substrate (pMA1), a P4 genome-sized plasmid containing only that region of P4, the cos site, necessary for encapsidation. Superinfection by P2 of a host carrying pMA30 under induced conditions resulted in a shift from large to small capsid production. P2 superinfection of a host carrying the cos plasmid pMA1 plus pMA30 under induced conditions yielded pMA1-transducing particles of P4 capsid size. These cloning-based analyses directly demonstrate that sid protein is the only P4 gene product required for small-capsid size determination. In the absence of the P2 O gene product no capsids of any size are assembled during solo infection by P2. Nevertheless, P2 Oam mutant superinfection of a host carrying pMA1 and pMA30 under induced conditions yielded small P4-sized transducing particles. We therefore propose that (i) the sid gene product competes with the O gene product to determine the assembly of small vs. large capsid sizes and (ii) both gene products probably function as temporary scaffolding proteins.

Base Sequence↗
PubMed1990

Resolution of recent evolutionary divergence among Escherichia coli from related lineages: the application of pulsed field electrophoresis to molecular epidemiology.

Escherichia coli infecting the urinary tract and other extraintestinal sites are often identical in many phenotypic and genotypic characteristics. To discriminate among pathogenic E. coli isolates, chromosomal DNA was digested with restriction endonucleases that recognize eight base pair sequences and the resulting 20-25 fragments were resolved by pulsed field gel electrophoresis (PFGE). Different restriction fragment profiles were detected for isolates obtained from different patients, including isolates of the same evolutionary lineage that were identical in electrophoretic type, serotype, and antibiotic sensitivities. In contrast, isolates obtained from separate sites of infection within the same patient had identical restriction profiles. These results indicate that PFGE can resolve recent evolutionary divergence within E.coli lineages and, consequently, offers a powerful new means for precisely performing molecular epidemiology. In addition, these studies provide genetic evidence that E. coli urinary tract infection within a given patient is typically due to the expansion of a single bacterial clone.

Biliary Tract Diseases↗
PubMed1990

Restriction fragment length polymorphisms among uropathogenic Escherichia coli isolates: pap-related sequences compared with rrn operons.

Among the adhesin-encoding virulence operons associated with uropathogenic Escherichia coli, only pap (pyelonephritis-associated pilus)-related gene clusters typically exhibit variation in their structure and chromosomal copy number. To access further such variability, we compared pap restriction fragment length polymorphisms (RFLPs) with those detected among rRNA (rrn) operons, which encode an essential host function unrelated to virulence. To place such findings in a phylogenetic perspective, the E. coli isolates were also characterized by using multilocus enzyme electrophoresis. Variation in the rrn RFLP profiles correlated with evolutionary divergence resolved by multilocus enzyme electrophoresis; isolates with identical rrn profiles represented the same or closely related electrophoretic types. In contrast, such isolates frequently had different pap-related RFLPs, indicating that these genetic variations have developed recently relative to the changes associated with essential rrn operons or metabolic enzymes. Despite such fluctuations, two lines of evidence indicate conditions under which the pap-related RFLPs can be stably maintained. First, for each of 20 patients with urosepsis, both the primary urinary tract isolate and the concurrent blood isolate were identical. Second, although obtained from different patients, some isolates representing the same electrophoretic type also had identical pap-related RFLPs. Thus, the genotypic diversity of this virulence adhesin operon was not generated during the course of acute infection or during laboratory manipulations. Since fecal E. coli isolates frequently carry chromosomally encoded pap-related gene clusters, these findings suggest that the intra- and interchromosomal recombination events generating the polymorphisms associated with the pap-related sequences likely occur among the E. coli of the commensal reservoir.

Base Sequence↗
PubMed1990

Isolated lipase and colipase deficiency in two brothers.

Two brothers of Arab origin, aged 15 and 10 years, with isolated congenital lipase and colipase deficiency are described. Both were normally developed with a history of passing greasy stools since early infancy. Both have remarkable steatorrhoea and low serum carotene and vitamin E concentrations. After exocrine pancreatic stimulation, lipase and colipase activities in the duodenal fluid were almost completely absent, while amylase trypsin, bile salt, and pH values were normal. No other aetiology for exocrine pancreatic insufficiency was found. This is the first report of congenital combined lipase and colipase deficiency in two brothers.

Adolescent↗
PubMed1990

Lightness and brightness over spatial illumination gradients.

We extended our studies of lightness and brightness in complex scenes to cathode-ray-tube simulations of an array of 35 gray reflective patches under spatially varying illuminants. There were three illuminance profiles, an abrupt step, a linear gradient, and a simulation of side illumination, with nine steepnesses of each. In half the sessions observers adjusted a test patch at one end of the illumination gradient in order to match the lightness of a standard patch at the other end of the gradient. In the remaining sessions they matched the brightness of the test patch to that of the standard. For all three illuminance profiles the lightnesses of the patches matched when they had approximately the same simulated reflectance; i.e., there was excellent lightness constancy even though the illuminance gradients were clearly visible.

Adaptation, Ocular↗
PubMed1990

Long-term follow-up review of 31 children with severe closed head trauma.

Thirty-one children aged 3 to 15 years were followed for 5 to 11 years after suffering severe closed head trauma which caused coma for 1 week or more (median duration of coma 3 weeks). One patient remained in a persistent vegetative state until his death 9 years later. The other 30 recovered consciousness and were discharged. All suffered diminution of their abilities, and 24 of them had major permanent disability. The most common motor disabilities were pure spastic hemiparesis (seven cases), basal ganglia syndromes (four cases), ataxia (three cases), and a combination of hemiparesis and ataxia (five cases). Of the 30 patients, 26 regained independent ambulation, seven were epileptic, and 14 were dysarthric in various degrees. Only 10 had the cognitive ability to profit from the normal educational system, and none had attempted postsecondary education. Social problems were common. The worst outcomes were associated with intracranial bleeding and/or brain contusion seen on computerized tomography (CT) scans at the acute stage; the best were associated with normal CT scans. The degree of residual disability in these children seems no less than that of adults with trauma of similar severity.

Adolescent↗
PubMed1990

Connective tissue disease in southeast Georgia. A community based study of immunogenetic markers and autoantibodies.

HLA antigens, C4 allotypes and T cell antigen receptor (TcR)beta DNA polymorphisms were determined in a community based study of connective tissue diseases (CTD). HLA-B8, DR3 and C4A null phenotypes occurred frequently in Caucasian patients with CTD, especially those with systemic lupus erythematosus (SLE), but were also more commonly found among healthy white controls of this southeast Georgia community. TcR beta gene polymorphisms also showed differential segregation patterns between patients with SLE and scleroderma. High frequencies of ANA and anti-ssDNA antibodies occurred among apparently healthy family members and local controls. Genetic factors predisposing to CTD in a community setting appear to be similar to those reported from referral centers.

Alleles↗
PubMed1990

C4 null genes in American whites and blacks with myositis.

The frequencies of C4A and C4B alleles were determined in 66 adults with myositis in relation to HLA class I and II. In whites with myositis, the C4A*Q0 allele occurred in 13/31 (47%) as compared to 25/101 (25%) normal controls (p = 0.08, relative risk = 2.7). Only 11/35 (31%) of black patients with myositis had a C4A*Q0 allele compared to 11/55 (20%) of controls (p = NS, RR = 1.8). Thus, the MHC class III genes do not appear to be the primary genetic risk factors for myositis in adults.

Alleles↗
PubMed1990

Ornithine decarboxylase: an unreliable marker for the identification of population groups at risk for colonic neoplasia.

Ornithine decarboxylase (ODC) is the first and rate-limiting enzyme in the polyamine biosynthetic pathway. Polyamines have been studied as potential markers of neoplastic diseases, including colonic cancer. Previous studies have pointed out the possible value of this enzyme as a biochemical marker of colonic neoplasia, we studied 100 patients undergoing diagnostic total colonoscopy. There were 40 normal controls and 20 patients in each of the following groups: 1) family members of patients diagnosed as having colonic tumors, 2) patients with adenomas, and 3) patients with colonic adenocarcinoma. Six forceps biopsies were obtained from the normal-appearing sigmoid mucosa for the analysis of ODC. No difference was found among the four groups studied. We therefore conclude that ODC is unreliable for clinical use as a biochemical marker for the identification of population groups at risk for colonic neoplasia.

Adenocarcinoma↗
PubMed1990

The implicated and the immune: cultural responses to AIDS.

Unlike previous epidemics in American history, AIDS has spawned a host of creative works in the arts and mass media. Representations in the fine arts have emphasized perspectives of the insider or the "implicated," i.e., people with AIDS, while commercial programs and performers in popular culture have adopted the vantage point of the "immune," viewing AIDS as emblematic of a stigmatized "other." These cultural responses embody tensions between contemporary and traditional approaches to social life. Some television and commercial films are beginning to portray AIDS from the "implicated" perspective, however; this tentative change suggests that the epidemic is becoming more broadly experienced in the United States.

Acquired Immunodeficiency Syndrome↗
PubMed1989

C4A gene deletion and HLA associations in black Americans with systemic lupus erythematosus.

In North America and European Caucasoids with systemic lupus erythematosus (SLE) there is an increased frequency of a C4A, CYP21A gene deletion, largely associated with the HLA-B8,DR3,C4A*QO extended haplotype. There have been no consistent HLA associations reported for SLE in blacks, although an increased frequency of serologically determined C4A null alleles has been reported in two studies. We studied 79 black American SLE patients and 68 black controls by restriction fragment length polymorphism analysis to determine if a C4A gene deletion was a genetic risk factor for SLE. Moreover, the nature of the deletion and any HLA phenotypic associations were sought. Nineteen of 79 (24%) patients compared to 5 of 68 (7.4%) controls had a phenotypic C4A,CYP21A gene deletion (P = .005; RR = 4). A homozygous deletion in four patients gave a genotypic frequency of 23/158 (14.5%) SLE patients vs 5/136 (3.7%) controls (P = .001; RR = 4.5). The deletion was associated with HLA-DR2 (P = .03) and HLA-DR3 (P = .03). Moreover, all subjects with the deletion had HLA-DR2 or DR3 (P = 7.7 x 10(-6). HLA-B44 was also associated with the deletion (P = .02), and eight of the nine HLA-B44 positives also carried HLA-DR2. HLA-B8 approached significance (P = .08) and was always accompanied by HLA-DR3. Finally, this black population demonstrated a unique C4B gene size polymorphism with 80% C4B "short" as compared to the 40% C4B "short" frequency reported in whites. We conclude that a large C4A,CYP21A gene deletion, particularly associated with the HLA-B44, -DR2, and -DR3 alleles, is the strongest genetic risk factor thus far identified for SLE susceptibility in black Americans. Furthermore, the unique preponderance of the C4B "short" gene form may be a factor in the actual formation of the deletion.

Black People↗
PubMed1989

Vasotocin improves intelligence and attention in mentally retarded children.

In mentally retarded (MR) prepubertal children, investigated both before and after six months of treatment, synthetic arginine vasotocin (AVT) (10(-6) mg/day/0.1 ml, intranasally), but not oxytocin or saline alone, significantly increased the intelligence quotient (IQ) and improved the attention parameters without affecting the short-term memory. Taking into account both the psychometric results and the clinical observations, the effects of AVT could be mainly explained by assuming the improvement of attention. Since there was a significant inverse correlation between the pretreatment levels of the IQ and attention scores and their increase after AVT, and since the AVT effects tend to be more intense in autistic children, we hypothesize that the more affected the attention mechanisms, the more they are sensitive to AVT. The present results are tentatively explained by the paradoxical sleep-enhancing properties of AVT, mechanisms by which AVT could improve the brain plasticity in MR subjects and by this, the attention performance.

Attention↗
PubMed1989

Molecular epidemiology of adhesin and hemolysin virulence factors among uropathogenic Escherichia coli.

The pap, prs, pil, and hly operons of the pyelonephritic Escherichia coli isolate J96 code for the expression of P, F, and type 1 adhesins and the production of hemolysin, respectively; the afaI operon of the pyelonephritic E. coli KS52 encodes an X adhesin. Using different segments of these operons as probes, colony hybridizations were performed on 97 E. coli urinary tract and 40 fecal clinical isolates to determine (i) the presence in the infecting bacteria of nucleotide sequences related to virulence operons, and (ii) the phenotypic properties associated with such sequences. Coexpression of P and F adhesins encoded by pap-related sequences was detected more frequently among isolates from patients with pyelonephritis (32 of 49, 65%) than among those with cystitis (11 of 48, 23%; P less than 0.0001) or from fecal specimens (6 of 40, 15%; P less than 0.0001). Therefore, the expression of both adhesins appears to be critical in the colonization of the upper urinary tract. In contrast, afaI-related sequences were detected significantly more frequently among isolates from patients with cystitis, suggesting that this class of X adhesin may have a role in lower urinary tract infections. Urinary tract isolates differed from fecal isolates by a low incidence of type 1 adhesin expression among pil probe-positive isolates. hly-related sequences were only detected in pap probe-positive isolates. The frequency of hemolysin production among pap probe-positive isolates was not associated with a particular pattern of infection. The distribution of these virulence factors was similar in the presence or absence of reflux, indicating that structural abnormalities of the urinary tract did not facilitate colonization by adhesin-negative isolates.

Adhesins, Escherichia coli↗